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Slow Initial β-lactam Infusion With High-dose Paracetamol to Improve the Outcomes of Childhood Bacterial Meningitis (INFU/PARA)

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ClinicalTrials.gov Identifier: NCT01540838
Recruitment Status : Completed
First Posted : February 29, 2012
Last Update Posted : February 28, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

February 23, 2012
February 29, 2012
February 28, 2017
February 2012
February 2017   (Final data collection date for primary outcome measure)
Mortality [ Time Frame: On day 7 from the institution of treatment ]
All patients should stay in hospital ≥7 days.
Same as current
Complete list of historical versions of study NCT01540838 on ClinicalTrials.gov Archive Site
  • Mortality [ Time Frame: On days 14, 21, and 28 from the institution of treatment. ]
  • Status on the modified Glasgow Outcome Scale [ Time Frame: Examined on days 7, 14, 21, and 28 since institution of treatment ]
    Scores from 5 to 1
  • Death or any sequelae [ Time Frame: Examined on days 7, 14, 21, and 28 since institution of treatment ]
    Defined as any severe neurological sequelae, or hemi- or monoparesis, or ataxia, or psychomotor retardation of any degree, or any hearing impairment. Hearing is deemed impaired if the better ear fails to detect a threshold of 40 dB. The cut-off levels for moderate and severe hearing impairment are 60 dB and 80 dB, respectively.
  • A change in hearing threshold compared to the first test result [ Time Frame: Examined on days 7, 14, 21, and 28 since instituion of treatment ]
    Hearing thresholds are determined by an independent observer on the bases of the BERA register, for each ear separately.
  • Death or severe neurological sequelae [ Time Frame: Examined on days 7, 14, 21 and 28 since institution of treatment ]
    Severe neurological sequelae are defined as blindness, tetraplegia/paresia, hydrocephalus requiering a shunt and severe prychomotor retardation
  • Deafness [ Time Frame: Examined on days 7, 14, 21 and 28 since initiation of treatment ]
    Defined as a hearing threshold >80dBs in the better ear.
Same as current
Not Provided
Not Provided
 
Slow Initial β-lactam Infusion With High-dose Paracetamol to Improve the Outcomes of Childhood Bacterial Meningitis
Slow Initial β-lactam Infusion With High-dose Paracetamol to Improve the Outcomes of Childhood Bacterial Meningitis, Especially of Pneumococcal Meningitis, in Angola.

The main purpose of this trial is to test if mortality of childhood bacterial meningitis can be reduced by slow, continuous infusion of cefotaxime initially, instead of the traditional bolus administration four times daily (qid), combined with high-dose paracetamol orally, when both treatments are executed for the first 4 days. The series will be collected at Hospital Pediátrico David Bernardino, Luanda, Angola.

The recruitment of patients begins, the conditions permitting, in early 2012. The criteria for patient participation is a child at the age of 2 months to 15 years who presents with the symptoms and signs suggestive of bacterial meningitis, for whom a lumbar puncture is performed, and the cerebrospinal fluid analysis suggests bacterial meningitis.

The principal objective of the study is to examine if mortality of childhood bacterial meningitis can be reduced by slow continuous infusion of cefotaxime combined with high-dose paracetamol orally for the first 4 days (instead of the traditional qid administration of cefotaxime without concomitant paracetamol). Children qualifying for entry (see criteria below), whose guardian has given informed consent,will be randomized into 2 treatment arms (see details below)and receive the treatments in a double blind fashion (see details below). Primary and secondary outcomes (detailed below) will be evaluated according to predefined criteria and time points (see below).

Results will be analyzed for all patients in ITT datasets and in prespecified subgroups (etiology, nutritional status, etc.) in both crude and adjusted analysis. The efficacy results will be expressed as OR with 95% confidence intervals.

Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Bacterial Meningitis
  • Drug: Infusion with paracetamol
    The administration of 250 mg/kg/24 hours cefotaxime during the first 4 days as continuous intravenous infusion, each single infusion lasting for 12 hours (to prevent degradation of the agent), combined with high-dose paracetamol orally; the first dose is 30 mg/kg, then 20 mg/kg every 6 hours for 4 full days.
    Other Name: paracetamol=acetaminophen
  • Drug: Bolus without paracetamol
    The control intervention consists of 250 mg/kg/24 hours cefotaxime administered traditionally with intermittent i.v. boluses and the place bo of paracetamol orally, both repeated every 6 hours (qid) for 4 days.
    Other Name: Paracetamol=acetaminophen
  • Experimental: Infusion with paracetamol
    Cefotaxime is administered as 12 hourly infusions, together with high dose paracetamol (acetaminophen)
    Intervention: Drug: Infusion with paracetamol
  • Active Comparator: Bolus with placebo
    Cefotaxime is administered as bolus q.i.d. with a placebo of paracetamol
    Intervention: Drug: Bolus without paracetamol
Pelkonen T, Roine I, Cruzeiro ML, Pitkäranta A, Kataja M, Peltola H. Slow initial β-lactam infusion and oral paracetamol to treat childhood bacterial meningitis: a randomised, controlled trial. Lancet Infect Dis. 2011 Aug;11(8):613-21. doi: 10.1016/S1473-3099(11)70055-X. Epub 2011 May 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
375
February 2017
February 2017   (Final data collection date for primary outcome measure)

Eligibility criteria:

The study entry is assessed for all children at age 2 months - 15 years who present at these centers with the symptoms and signs suggestive of BM, and to whom lumbar puncture is performed.

Inclusion criteria:

All patients whose cerebrospinal fluid (CSF) turns out to be cloudy, positive by Gram staining or latex agglutination, or shows at least 50 leukocytes per mm3, will be enrolled in the study.

Participants: Exclusion criteria

Exclusion criteria:

  1. Trauma, or relevant underlying illness such as intracranial shunt, previous neurological abnormality (cerebral palsy, Down's syndrome, meningitis)
  2. Previous hearing impairment (if known)
  3. Immunosuppression, except HIV infection
  4. More than one parenteral dose of a pretreatment antimicrobial. Children with oral antimicrobials are included, this information being marked in the FOLLOW-UP sheet.
  5. Active tuberculosis (if tuberculotic meningitis is diagnosed during trial, it will be included in intention-to-treat (ITT) analysis)
  6. Known hepatic disease.
Sexes Eligible for Study: All
2 Months to 15 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
Angola
 
 
NCT01540838
INFU/PARA-BOLU/PLACE
Yes
Not Provided
Plan to Share IPD: Undecided
Plan Description: We are working on an agreement to share data with all the participants,
Heikki Peltola, Helsinki University
Helsinki University
Foundation for Paediatric Research, Finland
Study Director: Heikki O Peltola, MD, PhD Childrens Hospital of Helsinki University Central Hospital
Helsinki University
February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP